Post-translational modification of ribosomally synthesized peptides by a radical SAM epimerase in Bacillus subtilis.

Post-translational modification of ribosomally synthesized peptides by a radical SAM epimerase in Bacillus subtilis.
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通过枯草芽孢杆菌中的自由基SAM分配酶对核糖体合成的肽的翻译后修饰。

DOI:
10.1038/nchem.2714
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发表时间:
2017-07
期刊:
影响因子:
21.8
通讯作者:
Berteau O
Berteau O
中科院分区:
化学1区
文献类型:
--
作者:
Benjdia A;Guillot A;Ruffié P;Leprince J;Berteau O

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核糖体合成的肽是由l-氨基酸构建的,而d-氨基酸通常是非核糖体合成过程的标志。在这里,我们表明,模式细菌枯草芽孢杆菌能够产生一种新型的核糖体合成和后修饰的肽含有d-氨基酸,我们建议呼吁epipepepeptides。我们证明了两个[4Fe-4S]簇自由基SAM酶通过催化Cα H原子提取和使用关键的半胱氨酸残基作为H原子供体将l-氨基酸转化为它们的d-对应物。出乎意料的是,这些d-氨基酸残基被证明是诱导LiaRS表达的肽的生物活性所必需的,LiaRS是细菌细胞包膜应激反应系统的主要组分。存在于B中。在枯草芽孢杆菌和人类微生物组的几个成员中,这些表肽和自由基SAM差向异构酶拓宽了活生物体可接近的肽基结构的景观。
Ribosomally-synthesized peptides are built out of l-amino acids while d-amino acids are generally the hallmark of nonribosomal synthetic processes. Here we show that the model bacterium Bacillus subtilis is able to produce a novel type of ribosomally synthesized and post-translationally modified peptide containing d-amino acids that we propose to call epipeptides. We demonstrate that a two [4Fe-4S] clusters radical SAM enzyme converts l-amino acids into their d-counterparts by catalyzing Cα H-atom abstraction and using a critical cysteine residue as H-atom donor. Unexpectedly, these d-amino acid residues proved to be essential for the bioactivity of a peptide inducing the expression of LiaRS, a major component of the bacterial cell envelope stress response system. Present in B. subtilis and in several members of the human microbiome, these epipeptides and radical SAM epimerases broaden the landscape of peptidyl structures accessible to living organisms.
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